| Popis: |
The study of aging and neurodegenerative processes in the human brain necessitates a comprehensive understanding of its myeloarchitectonic, cytoarchitectonic, and vascular structures. While recent computational advances have enabled volumetric reconstruction of the human brain using stained slices, the standard histological processing methods have often led to tissue distortions and loss, making deformation-free reconstruction challenging. Therefore, the development of a multi-scale and volumetric imaging technique that can accurately measure multiple structures within the intact brain would be a significant technical breakthrough. In this work, we present the development of an integrated approach that combines serial sectioning Polarization Sensitive Optical Coherence Tomography (PSOCT) and Two Photon Microscopy (2PM) to provide label-free multi-contrast imaging of human brain tissue. Our method allows for the simultaneous visualization of scattering, birefringence, and autofluorescence properties of the post-mortem human brain. By utilizing high-throughput reconstruction of 4x4x2cm3 sample blocks and simple registration of PSOCT and 2PM images, we enable comprehensive analysis of myelin content, cellular information, and vascular structure. PSOCT provides mesoscopic images and enables quantitative measurement of those brain structures, while 2PM provide complementary microscopic validation and enrichment of cellular and capillary information. This combined approach reveals myelin density and structure maps of the whole brain block and supplies intricate vessel and capillary networks as well as lipofuscin-filled cell soma across cortical regions, providing insights into the myeloarchitectural, cellular and vascular changes associated with neurodegenerative diseases such as Alzheimer's disease (AD) and Chronic Traumatic Encephalopathy (CTE). |
